Leukemic Transformation of Myeloproliferative Neoplasms: Therapeutic and Genomic Considerations
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Purpose of Review
Although BCR-ABL1-negative myeloproliferative neoplasms (MPN) are chronic, clonal hematopoietic stem cell (HSC) disorders marked by proliferation of one or more myeloid lineages, a substantial proportion of patients transform to acute myeloid leukemia. Leukemic transformation (LT) from a pre-existing MPN carries a dismal prognosis. Here, we review recent genetic, biological, and clinical data regarding LT.
In the last decade, DNA sequencing has revolutionized our understanding of the genomic landscape of LT. Mutations in TP53, ASXL1, EZH2, IDH1/2, and SRSF2 are significantly associated with increased risk of LT of MPNs. Preclinical modeling of these mutations is underway and has yielded important biological insights, some of which have therapeutic implications.
Recent progress has led to the identification of recurrent genomic alterations in patients with LT. This has allowed mechanistic and therapeutic insight into the process of LT. In turn, this may lead to more mechanism-based therapeutic strategies that may improve patient outcomes.
KeywordsMyeloproliferative neoplasms Leukemic transformation Gene mutation Mouse model
Compliance with Ethical Standards
Conflict of Interest
Bing Li declares no conflict of interest.
John O. Mascarenhas reports grants from Incyte, Novartis, Janssen, Roche, CTI Biopharma, Pharmaessentia, Celgen, Merck, and Promedior.
Raajit K. Rampal reports personal fees from Incyte, Celgene, Jazz, Apexx, and Agios and grants from Constellation and Stemline.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: •• Of major importance
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